Kidney conundrum

A mysterious chronic kidney disease is afflicting a large number of people in India and Sri Lanka. Despite decades of studies, scientists are yet to pinpoint the cause of the disease. Vibha Varshney travels to Sri Lanka and analyses the state of research, while Richard Mahapatra and M Suchitra report from the hotspots of the disease in India

Everybody in Rautabhuin village in Cuttack knows the dilapidated mud house where a family of five sisters-in-law lives. All of them lost their husbands to a kidney disease between 1993 and 2005. Kuntala Naik, the eldest of the five, recounts the unexpected death of her husband, the first in the family to succumb to renal failure. “He was healthy. Only a month before his death he developed swelling in limbs and complained of severe fatigue,” Kuntala says. By the next year, his younger brother started showing similar symptoms. He was taken to the Shrirama Chandra Bhanj (SCB) Medical College in Cuttack city. It is the premier medical institute in Odisha. “The doctors diagnosed kidney failure. Despite the high cost of commuting, we wanted to take him to the hospital for dialysis. But the disease did not give us enough time to save him,” Kuntala recounts. Over the next few years, rest of the brothers died the same way, one after the other.

The disease has assumed almost epidemic proportions in this village in Narsinghpur block. Of the 94 households in Rautabhuin, 25 have at least one member with kidney problem, estimates Nabakishore Rout, the village secretary. The latest victim is six-year-old Kartikeswar Rout.

Doctors treating patients from Rautabhuin say their symptoms are similar to chronic kidney disease (CKD), a condition characterised by a gradual loss of kidney function. But none of them suffers from the common triggers of CKD, such as diabetes or hypertension. In the absence of a known cause, they have classified it as chronic kidney disease of unknown aetiology, or CKDu (see ‘What is CKDu’).

WHAT IS CKDu

Kidneys filter the blood and remove waste from the human body through urine. They also regulate electrolytes and blood pressure; maintain acid-base balance; and produce hormones such as calcitriol (which helps increase the level of calcium in the blood) and erythropoietin (that controls red blood cell production). In people suffering from chronic kidney disease (CKD), these functions get hampered. This leads to accumulation of fluids in tissues, causing swelling and extreme fatigue. Doctors usually prescribe anti-hypertension drugs and vitamins to prevent further damage. Once the kidney is damaged, there is no specific treatment. Patient has to depend on dialysis or opt for kidney transplant.

The disease has five stages. During initial stages, cellular changes lead to fibrosis in the kidney. This results in excess protein in the urine and high creatinine, a waste of body metabolism, in the blood. In the last two stages, the kidneys shrink—from about 9 cm to 2 cm. A person can function normally even if only 20 per cent of the kidney functions. This highlights the need for active surveillance of people who are at the risk of the disease. This will also help minimise further damage. Unlike CKD caused by hypertension and diabetes where the blood vessels of the kidney are affected, in CKD of unknown aetiology (CKDu) the damage is to tubules and interstitium of nephrons. This is where the waste laced with toxins is stored before being excreted. This damages the tissues. To understand CKDu and reduce its incidence, it is necessary to pin-point the toxin.

According to the Indian CKD Registry, maintained by the Indian Society of Nephrology since 2005, about 16 per cent of the 52,273 adult CKD patients in the database are classified as CKDu. The data shows that the category is the second biggest in CKD, following CKD caused by diabetes. The Indian CKD Registry also shows that most CKDu patients belong to low-income families. Routabhuin fits the bill. Government records show 70 per cent families in the village live below the poverty line.

Many more villages in Odisha are living under the curse. “Kidney problems are widespread in 29 of the 33 village panchayats in Narsinghpur,” says block development officer Bishnu Prasad Acharya. In 2009, following reports of people dying due to renal failure across Narsinghpur, non-profit Social Human Action for Rural Poor (SHARP) organised a CKD screening programme in three villages, including Rautabhuin. Of the 430 people who came for screening, 138 were diagnosed with CKD. In May this year, SHARP organised the programme in four villages, including the three covered in 2009. Nephrologists found 100 new CKD cases. None of them suffers from the known causes of CKD.

Such unusually high incidence of the disease prompted the regional wing of the Indian Council of Medical Research (ICMR), the Regional Medical Research Centre (RMRC) in Bhubaneswar, to survey 1,339 people in Narsinghpur between June and September this year. Its preliminary findings, to which Down To Earth has access, show 8-12 per cent people of the group suffer from CKD. “In most of the cases, we found that CKD was not related to hypertension or diabetes,” says S K Kar, director of RMRC. Experts at the institute say besides Cuttack, other districts such as Bhubaneswar, Jajpur, Balangir, Kalahandi, Jharsuguda and Koraput are also reporting high incidence of the disease.

ICMR has now identified Odisha as one of the two CKD hotspots. The other one is its southern neighbour, Andhra Pradesh.

In village Kanduluru in the coastal district of Prakasam, K Elamantha Rao, a 60-year-old farm hand, suffers from CKD. He came to know about his disease in 2008 at a medical camp organised by Nizam Institute of Medical Sciences (NIMS), Hyderabad. Almost 360 people from his village had got themselves tested at the camp; the results came positive for 81. Most people in Kanduluru are small farmers or farm labourers from scheduled castes and backward communities. “At least 19 villages in Prakasam have high burden of the disease,” says T Gangadhar, nephrologist at NIMS. His team screened 2,804 people for CKD and found 17.4 per cent of them were suffering from the disease. In some villages, the prevalence of CKD was 40 per cent, he says.

Medical screening in five coastal blocks in Srikakulam district by the team of Ravi Raju Tatapudi, former director of Medical Education in Andhra Pradesh, shows 17-26 per cent of the population suffer from CKD.

Gangadhar also says most CKD patients in the region do not suffer from the known causes—hypertension and diabetes.

Efforts to understand CKDu

Both Odisha and Andhra Pradesh have been reporting CKD for almost a decade, but health experts are yet to pinpoint the cause.

RMRC suspects painkillers or heavy metals like mercury, cadmium and arsenic could be the cause. But its study shows painkillers were used only by 14 per cent of the patients, which is not significant.

Researchers from Andhra Medical College, including Tatapudi, and Harvard Medical School in the US analysed water samples from Srikakulam. “Preliminary data pointed to a high level of silica contamination,” note the researchers in an abstract presented at the conference, Environment and Health-Bridging South, North, East and West, held in August 2013 in Switzerland. They implicate silica in the prevalence of the disease.

Gangadhar had found high levels of strontium and silica in water samples from Prakasam, but suggests that only silica could be linked to the disease. His study is yet to be published.

A recent study by the National Geophysical Research Institute (NGRI), Hyderabad, and WHO India, however, ruled out inorganic chemicals, such as silica, as the cause of kidney problems in Srikakulam and Prakasam. The team led by geologist D V Reddy of NGRI and A Gunasekar of WHO India measured major ions and trace elements in water. They found that groundwater in Srikakulam is less mineralised than that in Prakasam and the concentrations of inorganic chemicals were within the permissible limits for drinking water. The researchers also pointed out that while both the regions have a common problem of CKD, they are geologically, hydrologically, hydrochemically and socially different. “There is a need to understand the multi-factorial aetiology of CKD,” says Reddy. The study, carried out on the request of the Department of Science and Technology (DST) at the Centre, was published in Environmental Geochemistry and Health in March 2013.

For further investigation, DST has funded another comprehensive study in Srikakulam this year. Seven organisations in Andhra Pradesh—Nizam Institute of Medical Sciences, the National Institute of Nutrition, the Centre for Cellular and Molecular Biology, Andhra University, Association of Hydrologists of India, Andhra Pradesh State Ground Water Department and Aditya Institute—will look into the possible causes of kidney diseases. “The causative factors need to be analysed in a comprehensive way involving expertise from various departments,” says Gangadhar, the principal investigator of the study. Reddy and Tatapudi, who have extensively studied the problem in the region, are not part of the latest DST study.

The country’s premier medical research organisation ICMR has also decided to carry out studies to unravel the mystery of CKD. It is finalising studies and protocols. The head of ICMR’s task force, Vivekanand Jha, who is professor of nephrology at the Post Graduate Institute of Medical Education and Research in Chandigarh, says the studies will be divided into three major areas—environment, genetics and maternal nutrition. All these parameters are often linked to the disease. For example, Jha says, there is evidence that the children of undernourished mothers develop fewer nephrons. Maternal malnutrition could thus be a reason for CKD. If that is the case, improved nutrition would be a cheap method to control the disease, he says.

CKDu is not new to South Asia, nor is the controversy over what triggers it. Sri Lanka has been trying to unravel its mystery for the past two decades. Indian health experts can take their cue from Sri Lanka’s experience.

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